Impaired tumoricidal function of alveolar macrophages from patients with non-small cell lung cancer

Abstract

The capacity of alveolar macrophages and peripheral blood monocytes from patients with non‐small cell lung cancer to develop tumoricidal function after in vitro stimulation with different macrophage activators was investigated. Alveolar macrophages were found to be impaired in their ability to develop cytotoxic activity compared with either the peripheral blood monocytes from the same patients or alveolar macrophages from patients with nonmalignant lung disorders. This result was observed consistently under diverse culture conditions and with different macrophage activators including gamma‐interferon (γ‐IFN), granulocyte‐macrophage colony‐stimulating factor (GM‐CSF), phorbol myristate acetate, or endotoxin. The impairment in tumoricidal function observed in alveolar macrophages was not associated with reduced target cell binding compared to peripheral blood monocytes. Alveolar macrophages from patients with lung cancer were found to secrete significantly greater amounts of tumor necrosis factor (TNF) and interleukin‐1 (IL‐1) than either peripheral blood monocytes from the same patients or alveolar macrophages from the patients with nonmalignant disorders. These results are consistent with either different regulatory pathways for cytotoxicity and cytokine secretion in the alveolar macrophages of patients with lung cancer or diversity in the subpopulations of cells responsible for these functions.

IL‐8 induces exocytosis of arginase 1 by neutrophil polymorphonuclears in nonsmall cell lung cancer

“…Although only a minority of NSCLC cells expresses TNFa, tumor-associated macrophages (TAMs) also release TNFa in the tumor microenvironment. 23 In addition, TAMs upregulate IL-8 expression in NSCLC cells. 24 All these data indicate that infiltrating PMNs could find within lung cancer tissue a cytokine microenvironment, which induces their release of ARG1 and this hypothesis was substantiated by the presence of ARG1-depleted PMNs within NSCLC tumor tissue.…”

Surfactant strengthens the inhibitory effect of C-reactive protein on human lung macrophage cytokine release

“…In the study by Galve-de Rochemonteix et al, alveolar macrophages were obtained from patients with pulmonary cell carcinoma. Alveolar macrophages from patients with lung cancer have shown in vitro greater TNF-␣ and IL-1 secretion than healthy controls (3,28). In the present study, these Fig.…”

Pulmonary perspective: immunology in diagnosis and treatment of lung cancer

“…In vitro studies have shown that AMs from NSCLC patients had a reduced cytotoxicity against tumour target cells but produced increased amounts of TNF-α and IL-1, suggesting that cytotoxic activities other than these two cytokines are deficient [154]. This, however, is in contrast with data obtained by other groups, including our own, demonstrating a decreased production of cytotoxic mediators (IL-1, TNF-α, O 2 ) by AMs from cancer patients compared to healthy volunteers [155,156].…”

“…This, however, is in contrast with data obtained by other groups, including our own, demonstrating a decreased production of cytotoxic mediators (IL-1, TNF-α, O 2 ) by AMs from cancer patients compared to healthy volunteers [155,156]. This could result in a decreased tumoricidal activity, and has supported basic and clinical trials aiming to activate macrophage function [154]. Such efforts to activate the tumoricidal properties of macrophages in vivo with lymphokines, including IFN-γ, have so far produced disappointing results.…”

“…Part of this failure is probably related to the extremely short life of lymphokines and to their nonspecific binding to cells or matrix components in tissues outside the tumour. Several studies have documented in vitro the limited response of AMs from lung cancer patients to various stimuli, including IFN-γ and GM-CSF [154,157]. More recently, synthetic macrophage activators, such as muramyl di-or tripeptide (MDP or MTP), were entrapped within liposomes in order to prolong their life and improve their targeting [158].…”